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Iridium(III) complexes entrapped in liposomes trigger mitochondria-mediated apoptosis and GSDME-mediated pyroptosis.
- Source :
-
Journal of inorganic biochemistry [J Inorg Biochem] 2022 Mar; Vol. 228, pp. 111706. Date of Electronic Publication: 2022 Jan 05. - Publication Year :
- 2022
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Abstract
- In this report, a new ligand TFBIP (TFBIP = 2-(4'-trifluoromethyl)-[1,1'-biphenyl]-4-yl)-1H-imidazo[4,5-f][1,10]phenanthroline) and its three iridium (III) complexes [Ir(ppy) <subscript>2</subscript> (TFBIP)](PF <subscript>6</subscript> ) (Ir1, ppy = 2-phenylpyridine), [Ir(bzq) <subscript>2</subscript> (TFBIP)](PF <subscript>6</subscript> ) (Ir2, bzq = benzo[h]quinolone) and [Ir(piq) <subscript>2</subscript> (TFBIP)](PF <subscript>6</subscript> ) (Ir3, piq = 1-phenylisoquinoline) were synthesized and characterized. The cytotoxicity in vitro of the complexes toward several cancer cells was evaluated by 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) methods. The complexes show no cytotoxicity (IC <subscript>50</subscript>  > 100 μM) against these cancer cells. To enhance anticancer activity, these complexes were trapped in liposomes to form Ir1Lipo, Ir2Lipo and Ir3Lipo. The liposomes Ir1Lipo, Ir2Lipo and Ir3Lipo exhibit high or moderate cytotoxic activity. In particular, Ir1Lipo can effectively inhibit the cell growth with a low IC <subscript>50</subscript> value (< 10 μM) toward A549, HepG2, BEL-7402, B16, HeLa and SGC-7901 cells. Surprisingly, Ir1Lipo has no cytotoxic activity against the normal cell LO2 (IC <subscript>50</subscript>  > 100 μM). The apoptosis and pyroptosis were investigated. Ir3Lipo induces apoptosis with a high early apoptotic number of 37%. The reactive oxygen species (ROS) levels, mitochondrial permeability transition pore open and mitochondrial membrane potential were detected. The intracellular Ca <superscript>2+</superscript> concentration and release of cytochrome c were investigated. The expression of Bcl-2 (B-cell lymphoma-2) family proteins was explored by western blot. The antitumor activity in vivo of Ir1Lipo was evaluated with an inhibitory rate of 53%.<br /> (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Subjects :
- Antineoplastic Agents pharmacology
Cell Line, Tumor
Cell Proliferation drug effects
Humans
Iridium pharmacology
Liposomes pharmacology
Membrane Potential, Mitochondrial drug effects
Phenanthrolines chemistry
Pyridines chemistry
Quinolines chemistry
Reactive Oxygen Species metabolism
Apoptosis drug effects
Coordination Complexes chemistry
Iridium chemistry
Liposomes chemistry
Mitochondria metabolism
Pyroptosis drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3344
- Volume :
- 228
- Database :
- MEDLINE
- Journal :
- Journal of inorganic biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 35033830
- Full Text :
- https://doi.org/10.1016/j.jinorgbio.2021.111706